Induction of protective interferon-β responses in murine osteoblasts following <i>S. aureus</i>infection and the use of nucleic acid nanoparticles to enhance bacterial killing.

Abstract Staphylococcus aureusis the primary causative agent of osteomyelitis, a severe inflammatory bone infection. Treatment for osteomyelitis includes long-term antibiotic treatment, surgical debridement necrotic bone, or even amputation. is challenging due to an inability antibiotics penetrate tissue and resident cells that harbor intracellular bacteria, increased incidence infections associated with antibiotic-resistant S. aureusstrains. Following aureusinfection, including osteoblasts produce immune mediators regulatory factors. While type I interferons (IFNs) are best known their antiviral effects, it becoming apparent they impact susceptibility many pathogens. Here, we report elevated IFN-β levels in infected femurs mouse model osteomyelitis. RNA Tag-Seq analysis aureusinfected showed expression mRNA encoding ISGs. We confirmed rapid robust release protein production by following aureuschallenge. Furthermore, ISGs demonstrate this occurs secondary these cells. Importantly, have determined exposure aureus-infected markedly reduces viable bacteria harbored Finally, demonstrated delivery immunomodulatory nucleic acid nanoparticle (NANPs) scaffolds using lipid-based carriers murine osteoblasts. These NANPs promising agents could induce protective IFNs during aureusinfection be further functionalized antimicrobials kill aureus. This work was supported grant 1R01AI170012-01 IM MBJ from National Institute Arthritis Musculoskeletal Skin Diseases.